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色烯酮:抗阿尔茨海默病药物研发中的新兴支架。

Chromenone: An emerging scaffold in anti-Alzheimer drug discovery.

机构信息

Department of Pharmaceutical Chemistry, Delhi Pharmaceutical Sciences & Research University, Delhi 110017, India.

Pharmaceutical Chemistry Division, School of Medical and Allied Sciences, K.R. Mangalam University, Gurugram 122103, India.

出版信息

Bioorg Med Chem Lett. 2024 Oct 1;111:129912. doi: 10.1016/j.bmcl.2024.129912. Epub 2024 Jul 30.

Abstract

Alzheimer's disease (AD) presents a growing global health concern. In recent decades, natural and synthetic chromenone have emerged as promising drug candidates due to their multi-target potential. Natural chromenone, quercetin, scopoletin, esculetin, coumestrol, umbelliferone, bergapten, and methoxsalen (xanthotoxin), and synthetic chromenone hybrids comprising structures like acridine, 4-aminophenyl, 3-arylcoumarins, quinoline, 1,3,4-oxadiazole, 1,2,3-triazole, and tacrine, have been explored for their potential to combat AD. Key reactions used for synthesis of chromenone hybrids include Perkin and Pechmann condensation. The activity of chromenone hybrids has been reported against several drug targets, including AChE, BuChE, BACE-1, and MAO-A/B. This review comprehensively explores natural, semisynthetic, and synthetic chromenone, elucidating their synthetic routes, possible mode of action/drug targets and structure-activity relationships (SAR). The acquired knowledge provides valuable insights for the development of new chromenone hybrids against AD.

摘要

阿尔茨海默病(AD)是一个日益严重的全球健康问题。近几十年来,由于具有多靶点潜力,天然和合成色酮已成为有前途的药物候选物。天然色酮包括槲皮素、香豆素、虎杖苷、山奈酚、伞形酮、补骨脂素、花椒毒素和 methoxsalen(花椒毒素),以及合成色酮杂合体,如吖啶、4-氨基苯基、3-芳基香豆素、喹啉、1,3,4-恶二唑、1,2,3-三唑和他克林,都因其潜在的治疗 AD 作用而被研究。用于合成色酮杂合体的关键反应包括珀金和佩克曼缩合。已经报道了色酮杂合体对多种药物靶点的活性,包括 AChE、BuChE、BACE-1 和 MAO-A/B。本综述全面探讨了天然、半合成和合成色酮,阐明了它们的合成路线、可能的作用机制/药物靶点和构效关系(SAR)。所获得的知识为开发针对 AD 的新型色酮杂合体提供了有价值的见解。

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